PROJECT PLAN Flashcards
What is the mortality rate of pancreatic ductal adenocarcinoma (PDAC)?
> 90%
PDAC is known for its aggressive nature and poor prognosis.
At what mean age are patients typically diagnosed with PDAC?
71 years
There is a noted increase in early onset cases in patients under 50.
What are the categories of PDAC management and treatment?
- Surgically resectable cancer
- Potentially resectable tumour
- Metastatic disease
What is the overall survival rate for patients with resected PDAC after completing post-surgical chemotherapy?
40% (3 years), 20% (5 years)
These rates highlight the importance of effective post-surgical treatment.
What factors contribute to the failure of treatment in PDAC?
- Development of resistance
- Heterogeneity of tumour cells
- Tumour microenvironment
True or False: Progress has been made in the early diagnosis and treatment of PDAC.
False
There has been little progress compared to other cancer types.
What is the significance of exhausted and senescent T lymphocytes in PDAC?
They are enriched in the tumour center and contribute to resistance to immune checkpoint inhibitors.
What urgent need is identified in the management of PDAC?
- Identify markers for favourable survival outcomes
- Assess differences in tumour microenvironment based on age of onset
What is the main purpose of the project discussed?
Identify markers predictive for positive response to therapeutic regimes at diagnosis.
What are the specific aims of the project?
- A. Multivariate correlation of tumour microenvironment heterogeneity with therapeutic response and age onset
- B. Assess the role of onset age in disease severity in vivo
What methodologies will be used to assess the immune profiling of the tumour microenvironment?
- Multiplex in situ transcriptomics
- Immunofluorescence
What is the Global Cancer Statistics 2020 ranking for PDAC?
14th most common cancer worldwide
What types of therapy are given to patients with borderline resectable PDAC?
Neoadjuvant therapy before surgical resection consideration.
What is a major reason for dismal results in immune checkpoint inhibitor therapy in PDAC?
Highly immunosuppressive tumour microenvironment
What is the relationship between early onset pancreatic cancer and smoking?
Higher incidence in countries with high smoking rates.
What are the two patient groups analyzed in the pilot study?
- Resectable tumour followed by adjuvant therapy
- Borderline resectable with neoadjuvant therapy
What is the hypothesis regarding tumours of different age onset?
They have different immune and mutation profiles.
What specific immune markers will be analyzed in the spatial immune profile?
- B cells (CD79a)
- CD4 and CD8 T lymphocytes
- T cell exhaustion markers (TCF1, PD1)
What is the purpose of combining immunofluorescence and RNAscope?
To perform phenotypic and functional analysis of immune profiling and cytokine mRNA expression.
What are the clinical outcome parameters analyzed in relation to immune profiles?
- Relapse Rate (RR)
- Disease Free Survival (DFS)
- Overall Survival (OS)
What preliminary findings suggest a correlation with improved overall survival in PDAC?
Percentage of cells expressing the T cell transcription factor TCF1 in the tumour centre.
What are cytotoxic T lymphocytes?
A type of immune cell that kills cancer cells and infected cells.
What is the significance of TCF1 and CD4 double-positive cells in cancer research?
They are associated with improved overall survival (OS) in patients.
What does a Kaplan Meier curve illustrate?
Overall survival (OS) rates over time for different patient groups.
